Something's Fishy

University of Pittsburgh researcher Dan Volz (center) and his crew on the north bank of the Monongahela, near the Hot Metal Bridge. (left to right: Drew Michanowicz, Samantha Malone and Chuck Christen)

Modern humans live in a chemical soup. Auto fumes and food preservatives, prescription drugs and polyester dust ... we eat man-made chemicals, drink them, inhale them and absorb them through our skin.

The evidence turns up in human blood and urine, where the synthetic molecules of some 500 different chemicals have been found. Thus we don't merely live in a chemical soup: Each of us is one.

A few years ago, University of Pittsburgh researcher C. Daniel Volz grew interested in another animal inhabiting roughly that same big soup. In 2007, he and his colleagues published an innovative study involving fish caught in Pittsburgh's three rivers. The study suggested that local fish were accumulating man-made chemicals that mimic estrogen. By implication the rivers themselves -- where we get most of our drinking water -- must be rife with those substances too.

Another disturbing finding: Some of the fish in the study were found to be "intersex," or of indeterminate gender. Some carried immature eggs in their testes.

Volz is one of a growing number of scientists studying those hormone-affecting chemicals, called "endocrine disruptors." The little-regulated substances are a volatile subject: Retailers like Wal-Mart have pulled suspected endocrine disruptors from shelves. This past January, one endocrine disruptor became subject to a partial federal ban.

The $689 billion chemical-manufacturing industry maintains that its products are safe. But the issue continues drawing attention: On Sept. 25, Volz will be among the speakers here at the Rachel Carson Homestead Association's annual Legacy Conference, titled "When Chemicals Disrupt: Managing Our Risks." Other speakers include Linda Birnbaum, who heads the National Institute of Environmental Health Sciences.

But even amid calls for further regulation, studies like Volz's raise more questions than they answer.

One mystery is the identity of the endocrine-disrupting chemicals. They're a subset of the roughly 100,000 synthetic compounds now in use, but no one knows what all of them are, or can even estimate how many there might be. As Volz puts it, "What is it in the fish that could do this?"

Another question is whether endocrine disruptors, harmful as they might be to aquatic life, truly endanger humans.

And then there's this dilemma: the chemicals' source. Some of the substances, like heavy metals and pesticides, are industrial or agricultural in origin. But others originate in everyday plastic, in pharmaceuticals, in personal-care products like toothpaste and shampoo.

They originate, in other words, with our modern way of life. And Volz worries that we might be putting ourselves, along with other creatures, even deeper into the soup.

Mark Brewer

We have met the fish, and they are us: (1) Fish -- along with other foods, beverages, pharmaceuticals and personal-care products we consume -- mostly go (2) down the drain, along with any chemicals they contain. Via sewage treated or untreated, much of it ends up (3) in the river, where we get (4) our water.

This Gland Is Your Gland

Volz heads the health-risk assessment branch of the Department of Environmental and Occupational Health in Pitt's Graduate School of Public Health. An assistant professor, he's a nationally quoted authority on water pollution, and has testified before Congress on the dangers of coal waste. In 1997, after a career in environmental consulting, at age 44, the Cranberry native returned to Pitt to study public health.

"You get to a point in life you want to have a legacy, [where] work is more than a job, or even a career," says the amiably blunt Volz, now 55. "It becomes a vocation."

In 2004, colleagues from Rutgers University sent Volz documentation of a conference they'd run -- the first international scientific symposium on endocrine disruptors and the environment. "It was about a 4,000-page book," says Volz. "I looked at it and said, 'This is the thing that I should be doing.'"

Endocrine disruptors affect an especially sensitive aspect of the human body. The endocrine system is a series of glands, the hormones they make, and the receptors sensitive to those hormones: the pituitary, adrenal and thyroid glands, for instance, along with the ovaries, testes and pancreas.

Hormones are chemical messengers, carrying information from one set of cells to another. They're especially crucial in the development of fetuses and young children, and they regulate things like growth, metabolism and reproductive ability.

Unlike many chemicals that researchers study, endocrine disruptors are defined by what they do, not what their composition is. They act as "false messengers," playing the part of hormones while sending messages your body doesn't intend. Some can mimic such hormones as estrogen, or the male sex hormone androgen. Others prevent hormones from binding to their receptors, blocking messages your body has sent. The chemicals can also stimulate or inhibit production of natural hormones.

Lab research on animals suggests that such disruptions can cause things like: birth defects; cancers of the testicles and breast; behavioral and developmental problems; early puberty in females; lowered sperm counts; and heightened risk of obesity, diabetes and even chromosomal damage.

Some endocrine disruptors occur naturally -- in plants like soybeans, for instance. But our bodies have evolved defenses to many of them, and most break down rather quickly once inside us. By contrast, the endocrine disruptors that most concern scientists like Volz are less than a century old. They're man-made, mostly from fossil-fuel stock like oil, natural gas or coal. And once created, many persist in us and in the environment. (Click here for tips on how to avoid endocrine disruptors in the home.)

These chemicals have been widely used for decades. Among the world's highest-production chemicals, for example, is Bisphenol-A (BPA), an endocrine disruptor used in plastics and epoxies. You can find it in baby bottles and sippy cups, the linings of metal cans for food and beer, even dental sealants. As with many endocrine disruptors, its name appears on no product label, because it's part of the container itself. Other identified endocrine disruptors are often considered too insignificant, as ingredients, to be listed.

Many endocrine disruptors are "plasticizers," used to make plastic soft and flexible, as in water bottles. Six kinds of plasticizer, commonly used in things like vinyl shower curtains and rubber duckies, were recently banned in baby products. (The European Union has had a similar partial ban since 1999.)

Many endocrine disruptors do not break down in the environment, but rather pass through water and air, and through the food chain, as one organism devours another.

Volz got the idea to study fish from the same Rutgers colleagues who clued him to endocrine disruptors. He'd worked for them in Alaska's Aleutian Islands in the '90s, studying whether radionucleides from past atomic testing still endangered fish, or the indigenous people who ate them.

Volz's study showed that the risk from radiation had dissipated. But the project taught him how fish can accumulate poisons in their bodies. When he learned about endocrine disruptors, a light went on.

The key, essentially, was plumbing. When humans consume a substance contaminated with a chemical, or rub it on their skin, it eventually descends some drainpipe -- often in the bathroom -- and then heads for sewage plants. Ultimately, "[a]ll of this had to go down into the river -- and the river was the next town's drinking water," Volz says. "It became immediately apparent to me that this should be looked at in fish. I had an epiphany."

The fish study Volz and his colleagues at Pitt embarked on in 2005 was unusual for its time, and would perhaps have been unthinkable a few decades earlier. For one thing, he involved the community, recruiting local fishermen -- some of whom subsisted partially on their catches -- to provide research subjects. Anglers, Volz notes, usually catch bigger fish than scientists -- and bigger fish have accumulated more toxins, which tend to build up in fat.

Moreover, rather than targeting a single toxin in these channel catfish and white bass, the researchers explored a whole suite of them.

Small chunks of each fish's skin, fat and flesh were ground up in the lab. Extracts were mixed with breast-cancer cells, which flourish in the presence of estrogen, the female sex hormone.

Researchers found that some fish tissue was 67 percent as good at making cancer cells grow as pure estrogen would have been. The effect was most pronounced in fish caught at sites where raw sewage frequently pours into the rivers -- including areas near the Point and the Braddock Dam. (Fish caught upstream on the Allegheny, near Kittanning and the Highland Park Dam, had lower concentrations.)

The study, funded largely by the Heinz Endowments, received national attention. An article in Scientific American was headlined "Bringing Cancer to the Dinner Table" -- a somewhat misleading phrase, since the study wasn't about cancer per se. But the research, first published in the proceedings of the 2007 National Conference on Environmental Science and Technology, earned Volz invitations to "the rubber-chicken circuit," he jokes, including a talk at the American Public Health Association Conference.

Colleagues praised the study's approach. "It's a great way to make the connection between a source of pollution, an environmental pollution and health effects," says Maryann Donovan, scientific director of the University of Pittsburgh Cancer Institute's Center for Environmental Oncology. "You get to see the circle of life. ... [Pollution] comes back to haunt you."

But if the study's methods were unusual, endocrine disruptors are an unusual pollutant.

In the 1970s, when Volz was a Pitt graduate student, "environmental health" mostly meant protecting workers from industrial toxins. True, in the wake of Rachel Carson's Silent Spring, the pesticide DDT had been banned. So had DES, a synthetic estrogen once prescribed to pregnant mothers and later linked to problems including vaginal cancer in their daughters. But while Volz says "incredible precautions" were taken to safeguard pharmaceutical workers from exposure to synthetic estrogens, for example, no laws shielded the rest of the world once the substances left the factory floor.

Slowly, researchers began looking at how pollutants affected the environment outside the manufacturing plant. Eventually, says Volz, "I crawled up the smokestacks and out the wastewater pipes and ventured into the larger world of environmental hygiene."

Meanwhile, researchers were no longer focusing exclusively on cancer. The 1996 book Our Stolen Future -- a best-seller about endocrine disruptors -- documented this shift. Co-author Theo Colborn, the environmental scientist who coined the term "endocrine disruptor," said researchers had finally begun to perceive other, more insidious effects of pollutants. Often, these involved seemingly healthy animals exhibiting abnormal traits, like the undersized penises in male alligators in Florida's Lake Apopka in the 1980s, years after a pesticide spill.

Colborn and others even speculated whether the declining sperm counts found in some countries were linked to environmental pollution. Likewise steep rises in testicular and breast cancers, trends dating to the post-war period when synthetics became an integral part of daily life.

Recent studies suggest the connections could be intimate: Harvard University researchers recently announced that blood levels of BPA in college students jumped 70 percent in a week when they switched from stainless-steel drink bottles to plastic (presumably from the chemical leaching into the water).

But Volz's study with breast-cancer cells and Pittsburgh's fish also addressed another issue: the uncountable array of chemicals polluting local rivers.

In Pittsburgh and elsewhere, when rainstorms flood aging sewer lines, the chemicals we've shed from our bodies or dumped down drains mix with other raw sewage and wash into the rivers. In Allegheny County alone, this happens about 75 times each year, sometimes for multiple days, at the region's approximately 500 river-bank sewer outlets. That's an estimated 16 billion gallons of untreated water annually.

Even the endocrine disruptors that reach wastewater plants, however, don't simply vanish: Because the facilities are not required to test for them -- and don't have a way to remove them anyhow -- they can end up even in treated sewage. If they are fortuitously processed out along with other pollutants, odds are the endocrine disruptors end up in sludge that gets used as fertilizer on feed crops. And when it rains on that farmland, the disruptors simply make their way to streams via runoff. (About a third of sewage sludge is burned, which can unleash other pollutants.)

In other words, many chemicals eventually return to the surface water that provides most of the nation's drinking water, helping make it a big accidental soup.

Ordinarily, pollution researchers study one suspected toxin at a time. But when the water is the chaotic effluvia of 200,000 homes, trying to tease out overall water quality by studying single chemicals is like trying to eat soup with a fork.By using breast-cancer cells, though, Volz's study was looking for all the estrogen, and the estrogen mimics, found in the water.

Upcoming research projects include testing the water itself to see what chemicals are in it, at what levels. Ultimately,he plans to test finished drinking water.

Shown Volz's study, a chemical-industry spokesman said he believed it overstated the impact of chemicals like Bisphenol-A. Naturally occurring hormones and pharmaceuticals are responsible for much more of the effect that Volz found, claims Steven Hentges, of the American Chemistry Council. "Many studies have shown that estradiol [a natural sex hormone in women] and the active ingredient in birth-control pills are present in water and have been shown to cause effects in the environment," he says.

Linda Birnbaum, who heads the federal National Institute of Environmental Health and Science, says Volz is moving in the right direction by exploring the entire "body burden" of chemicals animals take on. Chemicals might have an additive effect, with one impact stacking atop another. They also might react in combination, creating different impacts entirely. So if you're investigating the causes of a problem as complex as intersex fish, says Birnbaum, sussing one chemical at a time "isn't going to get us there."

Environmental advocates like Myron Arnowitt, Western Pennsylvania director of Clean Water Action, agree that new approaches are needed. Volz's research "[is] looking at a range of issues that are really the next set of things we're looking at in water quality," says Arnowitt.

Awareness of how endocrine disruptors harm wildlife has grown rapidly since 2003, when researchers from the U.S. Geological Survey discovered intersex bass in the Potomac River watershed. A 2009 USGS study, for instance, found that estrogen exposure puts fish at greater risk of disease and early death. Other researchers have found hermaphroditic frogs in suburban ponds.

There remains little doubt that the chemicals harm what scientists call "aquatic receptors." "That argument is closed," says Volz. And creatures like frogs and fishare "sentinels for human exposure" -- the canaries in the coal mine.

"Aquatic health and ecological health is a public-health issue," says Volz. "If other species can't survive, and especially other vertebrates -- we are fellow vertebrates."

Volz is outspoken about the need for more regulation of endocrine disruptors. "He's very committed to what he's doing, and he's not afraid to tell his story," says Maryann Donovan, of Pitt's Cancer Institute. But if you ask Volz whether such chemicals endanger people, he says, "I think the question is wide open." Even on fish, he adds, "I do not have enough information" about what individual chemicals do.

It's difficult to prove direct harm to humans without doing the sort of controlled experiments we can't ethically perform on people. And since humans and fish are both exposed to a whole range of chemicals outside the lab, it's impossible to tell precisely which chemicals might harm us.

Skeptics -- frequently the chemical industry and the researchers it employs -- often dismiss lab research. The doses there are too high to apply to real-world situations, they say. For instance, an American Chemistry Council handout states: "A 22-pound infant would have to drink more than 423 4-oz bottles per day" to exceed the European Food Safety Authority's safety standard for BPA.

Skeptics rely heavily on the toxicology truism that the dose makes the poison -- that even potentially harmful chemicals are safe if the exposure is limited enough.

"People are only exposed to very low levels of Bisphenol-A, levels that are far lower than any level that can cause a health effect," says the Chemistry Council's Steven Hentges.

But hormones play by different rules than toxic metals like mercury. If they're released at the wrong place and time -- during crucial stages in an animal's development -- even very small doses can have big consequences. Doses harmless to adults, for instance, might endanger children. It takes just 40 parts per billion of the naturally occurring hormone MIS, for example, to produce male sexual organs in the human embryo. Making the effects harder to trace, the results of such exposure might be long delayed, as in the early puberty experienced by female mice exposed to BPA in vitro. (Hormones are essentially the same chemicals in all organisms, whether human, animal or plant.)

Increasingly, research is driven largely by testing equipment sensitive to a single part per trillion or less. For instance, according to the Milwaukee Journal-Sentinel, which has conducted lengthy reviews of scientific studies, some tests have found BPA to harm animals at dosages as low as 25 parts per trillion. Meanwhile, lab tests have detected up to 8 parts per billion of BPA leaching from heated baby bottles.

An early warning in endocrine-disruptor research came in the late 1980s, when Tufts University researchers discovered that breast-cancer cells they hadn't dosed with estrogen were proliferating wildly. The reason, they learned, was that the estrogen mimic p-nonylphenol was leaching from the plastic test-tube caps.

Concern is growing about possible low-dosage impacts on humans. Frederick vom Saal is a reproductive biologist and pioneering researcher on endocrine disruptors at the University of Missouri-Columbia. He's found that children 6 years old have 10 times higher levels of a Bisphenol-A byproduct in their urine than did mice dosed with the chemical on purpose. And those mice later contracted cancer and other health problems.

Some scientists have concluded that mice might be more susceptible to estrogens than humans. But then human children might be more susceptible than adults, because they have different metabolisms.

In a report issued in June, the physicians' group The Endocrine Society states that there's enough evidence to consider endocrine disruptors "a significant concern to public health." The group recommends "regulation seeking to decrease human exposure to the many endocrine-disrupting agents."

Risky Business

But regulation is seldom simple. For one thing, the chemical-manufacturing industry lobbies hard against it. In 2008 alone, the industry gave $3.1 million in campaign contributions. About 10 percent of that came from the American Chemistry Council, the Arlington, Va.-based trade group that's often the industry's public voice.

Moreover, U.S. laws are written to require proof of harm to humans before regulation can kick in. Consider the BPA debate.

BPA was invented around 1890, and in the 1930s was discovered to be an artificial estrogen. Since the 1950s, it's been used in things like epoxy-resin linings for metal cans (it prevents corrosion and food contamination). It's also used to make rigid polycarbonate containers -- like baby cups -- transparent and shatterproof.

It's now ubiquitous. While BPA breaks down in the body quickly, a 2004 study by the federal Centers for Disease Control found it in 93 percent of urine samples tested. Apparently, we're constantly ingesting BPA. And over the past 20 years, a series of studies has found BPA to cause problems from cancer to neurological defects in lab animals at doses relevant to humans -- and at exposures much lower than what federal regulators have long deemed safe.

A number of government reports have proclaimed BPA safe, but those have been increasingly questioned. In 2007, during the business-friendly Bush administration, it was revealed that one such National Toxicology Program report had been largely written by staffers of Sciences International -- a consultant whose clients included major BPA manufacturers Dow Chemical and BASF.

Still, the public might remain confused: Last year, two reports from federal agencies seemed to contradict each other. First, the Food and Drug Administration asserted that BPA exposure levels were safe. Then a National Toxicology Program report announced that there was "some concern" about BPA's effects at current human exposures, especially for fetuses, infants and children.

Later, the FDA's own science board concluded that the FDA report had ignored key evidence of low-dosage harm, and told the agency to rework its risk assessment. And the Milwaukee Journal Sentinel reported that the FDA's endorsement of BPA was based primarily on two studies paid for by chemical-makers. In fact, the FDA report itself was largely written by the American Chemistry Council -- which continues to cite it as evidence BPA is safe.

While BPA is better publicized than most endocrine disruptors, environmental advocates say its regulatory situation is not unusual. Even in Europe, where regulatory standards are tougher, Bisphenol-A continues to be used. Meanwhile many of the other roughly 100,000 chemicals in use have yet to be studied much at all.

Moreover, industry is better funded than government and academia: The National Toxicology Program's entire operating budget ($192 million), for instance, is only about three times larger than the business-to-business advertising budget of a single big chemical manufacturer, Dow Chemical. So when regulators consult research on suspected toxins, the research is often funded by industry. In turn, industry cites the research as proof its products are safe.

Even sweeping regulatory changes can fail to fulfill their promises. In 1996, for example, a federal law was passed requiring the EPA to screen suspected endocrine disruptors. The agency has yet to study a single chemical.

Still, environmental groups working to ban BPA -- the National Resources Defense Council among them -- might feel they have some momentum. After all, Minnesota and Connecticut have passed partial BPA bans. So has Chicago.

But Volz, for one, doesn't like "the state-by-state approach." He'd prefer national standards -- and not just for one chemical at a time. "That's always the mistake we make," he says. "We need to regulate by class."

Volz believes that regulation of endocrine disruptors should be based on what's called "the precautionary principle." That principle says that if we know the rivers harbor potentially dangerous chemicals, we needn't wait for absolute proof of harm to humans to take action. "The research is running way ahead of the regulation at this point," he says.

Volz favors several approaches to start limiting the amount of endocrine-active substances in the waterways. He favors public-education campaigns (like the ones against litter and smoking) to get people to stop buying products that contain endocrine disruptors. Noting that most research on endocrine disruptors currently comes from Europe, he also favors boosting government research funding.

At the municipal level, he adds, "I am very much for expanding the list of chemicals that water systems should be testing for. Not that they necessarily have to remove them. But one needs a national database on which to make policy decisions."

Volz would like the U.S. to adopt a system like the one the European Union did in 2007. Called REACH , the European approach is based on the precautionary principle. It requires that manufacturers prove a new chemical is safe before bringing it to market.

Ultimately, Volz says, we should leave petrochemicals behind altogether, in favor of an approach that uses natural substances proven to be safe. "We need to start [getting] manufacturers to move past a regulatory mindset and into green chemistry."

Otherwise, if you get rid BPA, for example, how can you be sure the petrochemical you replace it with isn't just as bad -- or worse? That's assuming, you could even identify it: Volz, a public-health professor who's married to a physician, admits that sometimes even he can't tell when he's using a product that contains endocrine disruptors.

But Volz does not recommend panic. He doesn't, for instance, suggest foregoing tap water for bottled stuff. (Much bottled water is just processed tap water, after all, and likely contains chemicals that haven't been filtered out -- or that have leached from the plastic bottle itself.)

When in Pittsburgh, "I drink Pittsburgh tap water," he says, adding, "I think it's one of the best tap waters in the United States." (At home, in West Deer, he chlorinates and filters his well water.) He doesn't even recommend not eating fish, just limiting consumption. "We feel very strongly that having fish in your diet is essential," he says.

Still, Volz is resigned to treading that fine line between concern and fear familiar to environmental researchers. Of endocrine disruptors, he says, "If you don't know what the risk is, what do you tell people?"